Estimation of squeeze-film damping and inertial coefficients from experimental free-decay data

The results are given for an experimental program concerned with a parametric identification of the damping and inertial coefficients of a cylindrical squeeze-film bearing, through an analysis of transient response data. The results enable the operating range for which a linear model of the squeeze-film is appropriate to be determined. Comparisons are made between the estimated coefficients and theoretical predictions. Presentation is by courtesy of the Council of the Institution of Mechanical Engineers, London

Molecular Mechanisms and Antigen Receptor Requirements for Lymphocyte Adaptation to Intestinal Tissues

The intestine plays a crucial role in food digestion, nutrient absorption, water retention, and waste excretion. It contains the most populous immune cell reservoir in the body and is continuously exposed to a large and diverse number of diet- and microbiota- derived antigens. The highly stimulating luminal environment is separated from the core of the body, the lamina propria (LP), by just a single layer of epithelial cells. The intestinal immune system is thus tasked with being able to tolerate innocuous stimuli while mounting an effective response against potential pathogens in a controlled manner. To ensure appropriate balance between tolerance and resistance, T cells undergo tissue adaptation upon migrating from the gut-draining mesenteric lymph nodes (mLN) to the intestinal lamina propria and epithelium (IE). We sought to elucidate the transcriptional mechanisms and T cell receptor (TCR) signaling requirements of CD4+ T cell plasticity and adaptation in the intestinal tissues. Within the intestine, peripherally induced Foxp3+ regulatory T cells (iTregs), which are instrumental in limiting inflammatory responses to non-self antigen, are located primarily in the lamina propria. However, CD8aa-expressing intraepithelial CD4+ T cells (CD4- IELs), which also exhibit anti-inflammatory properties and depend on similar environmental cues, reside in the epithelium. Using intravital microscopy, we find distinct cell dynamics of intestinal Tregs and CD4-IELs. We addressed the molecular imprinting of the gut epithelium on T cells by integrating mouse genetics with single-cell RNAsequencing analyses. Transcriptionally, CD4+ T cells from mLN, LP and IE segregate based on the intestinal layer they occupy; trajectory analysis suggests a stepwise loss of CD4-programming and acquisition of an intraepithelial profile as CD4+ T cells adapt to the epithelium and convert to CD4-IELs. We found that upon migration to the epithelium, Tregs can lose Foxp3 expression and convert to CD4-IELs in a microbiota-dependent fashion, an effect in part attributed to loss of the CD4 lineage-defining transcription factor ThPOK. Treg fate-mapping coupled with RNA- and ATAC-sequencing revealed that the Treg program shuts down before an intraepithelial program becomes fully accessible at the epithelium. Ablation of Thpok results in premature acquisition of an IEL profile by mLN Tregs, partially recapitulating epithelium imprinting. Furthermore, we demonstrate that iTregs and CD4-IELs perform complementary roles in the regulation of intestinal inflammation in response to dietary antigen. To uncover the specific role of the T cell receptor in the process of CD4-IEL development, we combined in vivo fate-mapping and gene ablation models with single cell TCRsequencing. Single-cell TCR repertoire and transcriptomic analysis of intraepithelial CD4+ T cells revealed different extents of clonal expansion and TCR overlap between cell states; fully differentiated CD4-IELs from regulatory or conventional CD4+ T cells were the least diverse. Conditional deletion of TCR on differentiating CD4+ T cells or of MHCII on intestinal epithelial cells prevented CD4-IEL differentiation. However, TCR ablation on developed CD4-IELs did not affect their accumulation. Overall, our results reveal an inter- and intra-tissue specialization of anti-inflammatory CD4+ T cells shaped by discrete niches of the intestine. We uncovered the stepwise molecular mechanisms and TCR-signaling requirements for T cells to adapt to the intestinal epithelium. We found that the coordinated replacement of the circulating lymphocyte program with site–specific transcriptional and chromatin changes is necessary for tissue imprinting. Furthermore, our results indicate that local recognition of possibly a limited set of antigens is an essential signal for the differentiation and adaptation of T cells to the epithelium. Taken together, the work presented in this thesis demonstrates that a combination of genetic, TCR, and environmental triggers is crucial in driving T cell plasticity and adaptation to the tissues within the intestine

Symmetries and collective excitations in large superconducting circuits

The intriguing appeal of circuits lies in their modularity and ease of fabrication. Based on a toolbox of simple building blocks, circuits present a powerful framework for achieving new functionality by combining circuit elements into larger networks. It is an open question to what degree modularity also holds for quantum circuits -- circuits made of superconducting material, in which electric voltages and currents are governed by the laws of quantum physics. If realizable, quantum coherence in larger circuit networks has great potential for advances in quantum information processing including topological protection from decoherence. Here, we present theory suitable for quantitative modeling of such large circuits and discuss its application to the fluxonium device. Our approach makes use of approximate symmetries exhibited by the circuit, and enables us to obtain new predictions for the energy spectrum of the fluxonium device which can be tested with current experimental technology

Exploring CP Violation with B_d -> D K_s Decays

We (re)examine CP violation in the decays B_d -> D K_s, where D represents D^0, D(bar), or one of their excited states. The quantity $\sin^2(2\beta + \gamma)$ can be extracted from the time-dependent rates for $B_d(t) -> {\bar D}^{**0} K_s$ and $B_d(t) -> D^{**0} K_s$, where the $D^{**0}$ decays to $D^{(*)+}\pi^-$. If one considers a non-CP-eigenstate hadronic final state to which both D(bar) and D^0 can decay (e.g. $K^+\pi^-$), then one can obtain two of the angles of the unitarity triangle from measurements of the time-dependent rates for $B_d(t) -> (K^+\pi^-)_{D K_s}$ and $B_d(t) -> (K^-\pi^+)_{D K_s}$. There are no penguin contributions to these decays, so all measurements are theoretically clean.Comment: 15 pages, LaTeX, no figure

Two Types of K⁺ Channel Subunit, Erg1 and KCNQ2/3, Contribute to the M-Like Current in a Mammalian Neuronal Cell

The potassium M current was originally identified in sympathetic ganglion cells, and analogous currents have been reported in some central neurons and also in some neural cell lines. It has recently been suggested that the M channel in sympathetic neurons comprises a heteromultimer of KCNQ2 and KCNQ3 (Wang et al., 1998) but it is unclear whether all other M-like currents are generated by these channels. Here we report that the M-like current previously described in NG108–15 mouse neuroblastoma x rat glioma cells has two components, “fast” and “slow”, that may be differentiated kinetically and pharmacologically. We provide evidence from PCR analysis and expression studies to indicate that these two components are mediated by two distinct molecular species of K+ channel: the fast component resembles that in sympathetic ganglia and is probably carried byKCNQ2/3 channels, whereas the slow component appears to be carried by merg1a channels. Thus, the channels generating M-like currents in different cells may be heterogeneous in molecular composition

Can One Measure the Weak Phase of a Penguin Diagram?

The b -> d penguin amplitude receives contributions from internal u, c and t-quarks. We show that it is impossible to measure the weak phase of any of these penguin contributions without theoretical input. However, it is possible to obtain the weak phase if one makes a single assumption involving the hadronic parameters. With such an assumption, one can test for the presence of new physics in the b -> d flavour-changing neutral current by comparing the weak phase of B_d^0-{\bar B}_d^0 mixing with that of the t-quark contribution to the b -> d penguin.Comment: 20 pages, no figure

Primary crustal melt compositions: Insights into the controls, mechanisms and timing of generation from kinetics experiments and melt inclusions

We explore the controls, mechanisms and timing of generation of primary melts and their compositions, and show that the novel studies of melt inclusions in migmatites can provide important insights into the processes of crustal anatexis of a particular rock. Partial melting in the source region of granites is dependent on five main processes: (i) supply of heat; (ii) mineral–melt interface reactions associated with the detachment and supply of mineral components to the melt, (iii) diffusion in the melt, (iv) diffusion in minerals, and (v) recrystallization of minerals. As the kinetics of these several processes vary over several orders of magnitude, it is essential to evaluate in Nature which of these processes control the rate of melting, the composition of melts, and the extent to which residue–melt chemical equilibrium is attained under different circumstances. To shed light on these issues, we combine data from experimental and melt inclusion studies. First, data from an extensive experimental program on the kinetics of melting of crustal protoliths and diffusion in granite melt are used to set up the necessary framework that describes how primary melt compositions are established during crustal anatexis. Then, we use this reference frame and compare compositional trends from experiments with the composition of melt inclusions analyzed in particular migmatites. We show that, for the case of El Hoyazo anatectic enclaves in lavas, the composition of glassy melt inclusions provides important information on the nature and mechanisms of anatexis during the prograde suprasolidus history of these rocks, including melting temperatures and reactions, and extent of melt interconnection, melt homogenization and melt–residue equilibrium. Compositional trends in several of the rehomogenized melt inclusions in garnet from migmatites/granulites in anatectic terranes are consistent with diffusion in melt-controlled melting, though trace element compositions of melt inclusions and coexisting minerals are necessary to provide further clues on the nature of anatexis in these particular rocks.This work was supported by the National Science Foundation [grants EAR-9603199, EAR-9618867, EAR-9625517 and EAR-9404658], the Italian Consiglio Nazionale delle Ricerche, the European Commission (grant 01-LECEMA22F through contract No. ERAS-CT-2003-980409; and a H2020 Marie Skłodowska-Curie Actions under grant agreement No. 654606), the Italian Ministry of Education, University and Research (grants PRIN 2007278A22, 2010TT22SC and SIR RBSI14Y7PF), the Università degli Studi di Padova [Progetto di Ateneo CPDA107188/10 and a Piscopia—Marie Curie Fellowship under grant agreement No. 600376], the Australian Research Council (Australian Professorial Fellowship and Discovery Grants Nos. DP0342473 and DP0556700), and the National Research Foundation (South Africa; Incentives For Rated Researchers Program)